Respiratory syncytial virus (RSV) is the most important respiratory pathogen in infants, especially those born prematurely. It is also an important cause of disease in the elderly and immunosuppressed. There is no vaccine available to protect against RSV and "at risk" infants are presently treated by passive immunization. An effective small molecule drug that prevents RSV infection or ameliorates it would be of great value. The goal of this Phase I proposal is to develop a novel "replicon" system for screening potential antiviral compounds. The RSV replicon will be a genetically modified viral genome missing its three glycoprotein genes. The replicon will contain a drug-resistance gene to select cells that contain the replicon and a marker gene to easily assay virus replication and gene expression. This system will provide a useful molecular tool for rapid screening of compounds that inhibit any pathway involved in RSV genome replication, mRNA transcription, or translation. An RSV replicon will also be valuable for genetic studies of RSV and in efforts to use RSV as a vector. [unreadable] [unreadable]